Ginsenoside Rg1 suppresses paraquat‐induced epithelial cell senescence by enhancing autophagy in an ATG12‐dependent manner

Abstract Paraquat (PQ), as a widely used herbicide, is highly toxic to human. PQ‐induced pulmonary fibrosis is the main reason for respiratory failure and death. In PQ‐poisoned mice, we find abundant senescent epithelial cells in the lung tissues, which can contribute to the activation of pulmonary fibroblasts. Ginsenoside Rg1 (Rg1), the main active component of ginseng, possess beneficial properties against aging. In our work, we aimed to investigate the potential protective effects of Rg1 on PQ‐induced pulmonary fibrosis and the underlying mechanism. In vivo, the treatment of Rg1 can attenuate PQ‐induced pulmonary fibrosis and decrease senescence and senescence associated secretory phenotype (SASP) expression. In vitro, Rg1 can effectively eliminate senescent cells via apoptosis, but not normal cells. In addition, we demonstrate that Rg1 can enhance autophagy activity via inducing the expression of ATG12. Inhibition of autophagy via 3‐MA or transfection of the siRNA targeting ATG12 can impair the antiaging effect of Rg1. Taken together, our data implicates that Rg1 can protect pulmonary epithelial cells from PQ‐induced cellular senescence in an ATG12 dependent manner, which may provide a preventive and therapeutic strategy for PQ poisoning‐induced pulmonary fibrosis.